N-Acylsaccharins as Amide-Based Arylating Reagents via

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N‑Acylsaccharins as Amide-Based Arylating Reagents via Chemoselective N−C Cleavage: Pd-Catalyzed Decarbonylative Heck Reaction Chengwei Liu, Guangrong Meng, and Michal Szostak* Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, United States S Supporting Information *

ABSTRACT: Palladium-catalyzed decarbonylative Heck reaction of amides by chemoselective N−C activation using Nacylsaccharins as coupling partners has been accomplished. These studies represent only the second example of amideHeck reactions reported to date. A broad range of electronically diverse amide and olefin coupling partners is amenable to this transformation. Orthogonal site-selective Heck crosscouplings by C−Br/N−C cleavage and mechanistic studies are reported. This report introduces readily available, bench-stable, cheap, and benign N-acylsaccharins as aryl transfer reagents to access versatile aryl-metal intermediates.

T

he ability to perform selective functionalization reactions represents an enabling approach in organic synthesis. Since the first report in 1968, the Heck reaction has been established as one of the most powerful, chemoselective transition-metal-catalyzed transformations in organic synthesis.1,2 The classic Heck reaction furnishes functionalized olefins that are essential structural motifs for the synthesis of pharmaceuticals, organic materials, agrochemicals, and complex natural products in both academic and industrial settings.3 In particular, the use of feedstock alkenes as nucleophilic coupling partners has become a central tool for industrial manufacturing due to lowering the cost associated with olefin prefunctionalization.4 Methods have been reported for the cross-coupling of aryl halides,5a−d triflates,5e pseudohalides,5f and diazonium salts.5g,h While oxidative Heck reactions of carboxylic acids,6a phosphonic acids,6b and hydrocarbons6c have been developed, these methods require stoichiometric oxidants, proceed with limited scope or control of regioselectivity.2 In contrast, decarbonylative Heck reactions of stable aroyl electrophiles, such as esters and amides, remain a significant challenge (Figure 1).7 The advantages of using esters and amides in comparison with typical cross-coupling partners include (i) low cost; (ii) high stability; (iii) ready availability; and (iv) unprecedented potential for unconventional crosscouplings with orthogonal selectivity controlled by the facility of metal insertion into the C−O or C−N bond, which is not possible with unstable aroyl halides and anhydrides. Mechanistically, metal insertion into a weak C(CO)−X bond (X = O, N) enables the use of orthogonal coupling partners to aryl(aroyl) halides by decarbonylation of the initially formed acyl-metal species.8 However, despite the significant progress in the development of ester electrophiles for Heck reactions,7c,d the potential of amides as electrophilic coupling partners remains to be explored.2f,9 The chief challenge in activating the amide © 2016 American Chemical Society

Figure 1. Classic and aroyl electrophiles in the Heck reaction.

bond toward metal insertion is the amide nN → π*CO resonance (planar amides, ca. 15−20 kcal/mol).10 A general use of amides as coupling partners in the Heck reaction would have a potential to extend to the functionalization of biomolecules and large scale industrial olefinations using bench-stable, chemoselective, low-cost acid amide reagents. We have recently established the first decarbonylative Heck reaction of amides using N-glutarimides as coupling partners by steric distortion (Figure 2A).11 The first decarbonylative Suzuki and direct decarbonylative C−H activation of N-glutarimide amides using Ni and Rh catalysis have been developed.12 Recently, Ni-catalyzed decarbonylative borylation of amides by N−C cleavage has been accomplished.13,14 These reactions proceed via selective N−C insertion/decarbonylation, in which the facility of metal insertion is controlled by amide destabilization.15 Extensive studies on amide geometry provide additional evidence for the distortion of amides undergoing metal insertion.16 To expand the generality of decarbonylative Received: September 18, 2016 Published: November 17, 2016 12023

DOI: 10.1021/acs.joc.6b02294 J. Org. Chem. 2016, 81, 12023−12030

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The Journal of Organic Chemistry

Table 1. Optimization of Pd-Catalyzed Decarbonylative Heck Reaction of N-Acylsaccharins by N−C Cleavagea

Figure 2. (a) Decarbonylative N−C cleavage in amides. (b) Saccharins as electrophilic functional group transfer reagents.

Heck reactions by N−C cleavage, we considered Nacylsaccharins as bench-stable, amide-based, electrophilic coupling partners.17 Recently, N-acylsaccharins have emerged as efficient functional group transfer reagents in metal-catalyzed formylation18a and alkoxycarbonylation.18b We have developed conditions for the Suzuki-Miyaura cross-coupling of Nacylsaccharins to yield ketones with exclusive RC(O)− coupling selectivity (acyl transfer, Figure 2B).18c Herein, we report for the first time the Pd-catalyzed decarbonylative Heck reaction of N-acylsaccharins as electrophilic coupling partners by highly chemoselective N−C bond cleavage/decarbonylation. The following features of our findings are noteworthy: (i) low-price, availability, benign nature of saccharin; (ii) bench-stability and ease of crystallization of N-acylsaccharins, which allows to avoid sensitive intermediates during cross-couplings; (iii) excellent functional group tolerance and wide range of electronically diverse amide and olefin coupling partners that undergo this transformation; (iv) operationally simple, base-free, ligand-free conditions; (v) the first iterative Heck cross-couplings using carbonyl electrophiles by site-selective C−N/C−Br cleavage; (vi) most importantly, this report introduces readily available, benchstable, cheap N-acylsaccharins as aryl transfer reagents for metal-catalyzed transformations via metal-insertion/decarbonylation to access versatile aryl metal intermediates. Our studies demonstrate the highest reactivity of N-acylsaccharins in amide N−C cleavage discovered to date.18c The Heck cross-coupling of N-benzoylsaccharin (1) with nbutyl acrylate (2) was investigated as a model reaction to identify the most active catalyst system. Selected key optimization results obtained during the optimization studies are summarized in Table 1. Under our standard conditions, 1 underwent the decarbonylative N−C coupling in excellent 98% yield (entry 1). Notably, we found that the presence of halide salts had a negative impact on the reaction efficiency (entries 2−15).19 Similarly, the use of external nucleophiles7 (entries 4 and 13) and other solvents (entries 5−6 and 11−12) resulted in a diminished yield of the arylation product. We hypothesize that these effects are consistent with high electrophilicity of N-

entry

catalyst

1 2 3b 4c 5 6 7d 8e 9f 10b 11 12 13c 14d 15e 16g 17g,h,i 18g,i,j

PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2

ligand LiBr LiBr LiBr LiBr LiBr LiBr LiBr LiBr

LiBr

solvent

yield (%)

NMP NMP NMP NMP toluene dioxane NMP NMP NMP NMP toluene dioxane NMP NMP NMP NMP NMP NMP

98 63 41 N-glutarimides ≈ (Ar−CO)2O ≫ Ar−CO2R (Scheme 1C). (4) Electronic effects observed in the regioselectivity of the arylation with styrenes (styrene: ρ-value of 1.21, R2 = 0.99; amide: ρ+-value of 0.46, R2 = 0.90) indicate an increase in the arylation regioselectivity of electron-deficient 12025

DOI: 10.1021/acs.joc.6b02294 J. Org. Chem. 2016, 81, 12023−12030

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and dried. The crude product was purified by recrystallization (methanol or toluene) to give analytically pure product. All Nacylsaccharins are bench-stable solids with no decomposition observed while storing on benchtop at room temperature for a period of six months. General Procedure for Heck Cross-Coupling. An oven-dried vial equipped with a stir bar was charged with amide substrate (neat, 1.0 equiv), PdCl2 (typically, 3 mol %), and olefin (typically, 2.0 equiv), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. N-Methyl-2pyrrolidinone (NMP, 0.25 M) was added with vigorous stirring at room temperature, the reaction mixture was placed in a preheated oil bath at 160 °C, and stirred for the indicated time at 160 °C. After the indicated time, the reaction mixture was cooled down to room temperature and diluted with CH2Cl2 (5 mL). The sample was analyzed by 1H NMR (CDCl3, 500 MHz) and/or GC-MS to obtain conversion, selectivity, and yield using internal standard and comparison with authentic samples. In all examples reported in the manuscript 2,1/1,2-selectivity was obtained by analysis of the crude reaction mixture. Unless indicated otherwise, in all examples reported in the manuscript single olefin isomers were observed (E/Z > 98:2). Unless indicated otherwise, only monoarylated products were observed (mono/diarylation selectivity >98:2). All yields reported in the manuscript refer to isolated yields after purification by chromatography on silica gel (hexanes/EtOAc). Unless indicated otherwise, in all examples reported in the manuscript single olefin regioisomers were obtained after the purification. Representative Procedure for Heck Cross-Coupling. An ovendried vial equipped with a stir bar was charged with Nbenzoylsaccharin (neat, 57.5 mg, 0.2 mmol), PdCl2 (1.1 mg, 3 mol %) and n-butyl acrylate (51.3 mg, 2.0 equiv), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. N-Methyl-2-pyrrolidinone (0.25 M) was added with vigorous stirring at room temperature, the reaction mixture was placed in a preheated oil bath at 160 °C, and stirred for 18 h at 160 °C. After the indicated time, the reaction mixture was cooled down to room temperature and diluted with CH2Cl2 (5 mL). The sample was analyzed by 1H NMR (CDCl3, 500 MHz) and GC-MS to obtain conversion, selectivity, and yield using internal standard and comparison with authentic samples. 2,1/1,2 > 98:2. E/Z > 98:2. Purification by chromatography on silica gel (hexanes/EtOAc = 10/1) afforded the title product. Yield 82% (33.5 mg, 0.164 mmol). Colorless oil. Characterization data are included in the section below. 2.0 mmol scale coupling was performed according to the representative procedure using N-benzoylsaccharin (neat, 575 mg, 2.0 mmol), PdCl2 (11 mg, 3 mol%) and n-butyl acrylate (513 mg, 2.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M) at 160 °C for 18 h. 2,1/ 1,2 > 98:2. E/Z > 98:2. Purification by chromatography on silica gel (hexanes/EtOAc = 10/1) afforded 3a. Yield 79% (323 mg, 1.58 mmol). Colorless oil. Characterization data are included in the section below. 2.0 mmol scale coupling using styrene was performed according to the representative procedure using N-benzoylsaccharin (neat, 575 mg, 2.0 mmol), PdCl2 (18 mg, 5 mol%) and styrene (624 mg, 3.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M) at 160 °C for 18 h. 2,1/1,2 = 92:8. E/Z > 98:2. Purification by chromatography on silica gel (hexanes/ EtOAc = 10/1) afforded 3q. Yield 87% (314 mg, 1.74 mmol). White solid. Characterization data are included in the section below. N-Benzoylsaccharin (1a).24 Yield 95% (0.82 g). White solid. 1H NMR (500 MHz, CDCl3) δ 8.16−8.15 (d, J = 7.7 Hz, 1 H), 8.05−8.01 (m, 2 H), 7.96−7.94 (t, J = 7.9 Hz, 1 H), 7.80−7.78 (d, J = 8.3 Hz, 2 H), 7.70−7.67 (t, J = 7.1 Hz, 1 H), 7.55−7.52 (t, J = 7.7 Hz, 2 H). 13C NMR (125 MHz, CDCl3) δ 166.4, 157.5, 138.5, 136.4, 134.9, 133.9, 132.4, 129.6, 128.5, 126.4, 125.6, 121.3. MS = 287.0 (EI). N-4-Methoxylbenzoylsaccharin (1b).18c Yield 81% (0.77 g). White solid. 1H NMR (500 MHz, CDCl3) δ 8.16−8.15 (d, J = 7.7 Hz, 1 H), 8.01−8.00 (d, J = 4.2 Hz, 2 H), 7.95−7.92 (m, 1 H), 7.85−7.83 (d, J = 8.8 Hz, 2 H), 7.00−6.99 (d, J = 8.8 Hz, 2 H), 3.91 (s, 3 H). 13C NMR (125 MHz, CDCl3) δ 165.2, 164.7, 158.0, 138.5, 136.3, 134.9, 132.8, 126.3, 125.8, 124.4, 121.2, 114.0, 55.7. MS = 317.0 (EI).

olefins and electron-deficient amides. These preliminary studies are consistent with the initial metal insertion into the amide N−C bond;9 olefin insertion might be a kinetically relevant step in the reaction.22b The high reactivity of N-acylsaccharins (cf. glutarimides)11 bodes well for further applications in decarbonylative cross-couplings by amide N−C cleavage. We highlighted the synthetic utility of N-acylsaccharins as orthogonal cross-coupling partners in iterative site-specific C− N/C−Br cross-coupling (Scheme 2).23 The Heck crossScheme 2. Iterative Heck Cross-Coupling of NAcylsaccharins: C−N vs C−Br Cleavage

coupling of aryl bromides can be achieved by Pd/Pt-Bu3catalysis,5d,22c leaving the amide bond in N-acylsaccharins intact (Scheme 2, top). Alternatively, the amide N−C cross-coupling can be followed by the C−Br cleavage (Scheme 2, bottom). To our knowledge, this is the first sequential cross-coupling involving decarbonylative Heck reactions.2,3,7 The iterative cross-coupling is facilitated by the high reactivity of Nacylsaccharins18 and the ease of purification of intermediates by recrystallization.17 In summary, we have reported the first Pd-catalyzed decarbonylative Heck cross-coupling of N-acylsaccharins by chemoselective N−C cleavage. A variety of amide and olefin substrates is suitable for this reaction. The sequential Heck coupling of C−Br and C−N bonds has been demonstrated for the first time. N-Acylsaccharins are air-stable, crystalline solids that show comparable reactivity to N-glutarimide amides. The discovery that N-acylsaccharins serve as selective bench-stable aryl transfer reagents may enable the development of a broad range of novel metal-catalyzed transformations.

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EXPERIMENTAL SECTION

General Methods. All starting materials reported in the manuscript have been prepared according to the method reported previously.24 All compounds reported in this manuscript have been previously reported or are commercially available unless noted otherwise. Spectroscopic data matched literature values. General methods have been published.18c General Procedure for Amide Synthesis. An oven-dried flask (25 mL) equipped with a stir bar was charged with amine (typically, 3.0 mmol, 1.0 equiv), triethylamine (typically, 1.0 equiv), and N,Ndimethylacetamide (DMAc, typically, 0.75 M), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. Acyl chloride (typically, 1.0 equiv) was added dropwise to the reaction mixture with vigorous stirring at 0 °C, and the reaction mixture was stirred for 1 h at room temperature. After the indicated time, the reaction mixture was diluted with H2O (5 mL). The solid was collected by filtration, washed with Et2O (1 × 10 mL), 12026

DOI: 10.1021/acs.joc.6b02294 J. Org. Chem. 2016, 81, 12023−12030

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The Journal of Organic Chemistry N-4-Trifluorobenzoylsaccharin (1c).18c Yield 83% (0.89 g). White solid. 1H NMR (500 MHz, CDCl3) δ 8.17−8.15 (d, J = 7.7 Hz, 1 H), 8.06−8.05 (d, J = 4.0 Hz, 2 H), 7.99−7.95 (m, 1 H), 7.87−7.85 (d, J = 8.2 Hz, 2 H), 7.80−7.78 (d, J = 8.2 Hz, 2 H). 13C NMR (125 MHz, CDCl3) δ 165.5, 157.2, 138.4, 136.8, 135.7, 135.1, 134.9 (q, J2 = 32.8 Hz), 129.6, 126.6, 125.5 (q, J3 = 3.7 Hz), 125.2, 123.4 (q, J1 = 271.2 Hz), 121.4. 19F NMR (471 MHz, CDCl3) δ −63.22. MS = 355.0 (EI). N-4-Fluorobenzoylsaccharin (1d).18c Yield 79% (0.73 g). White solid. 1H NMR (500 MHz, CDCl3) δ 8.17−8.15 (d, J = 7.7 Hz, 1 H), 8.04−8.03 (d, J = 3.9 Hz, 2 H), 7.97−7.94 (m, 1 H), 7.85−7.82 (t, J = 8.6 Hz, 2 H), 7.22−7.19 (t, J = 8.6 Hz, 2 H). 13C NMR (125 MHz, CDCl3) δ 166.2 (d, J1 = 255.3 Hz), 165.2, 157.6, 138.4, 136.5, 135.0, 132.6 (d, J3 = 9.6 Hz), 128.6, 126.5, 125.5, 121.3, 115.9 (d, J2 = 22.3 Hz). 19F NMR (471 MHz, CDCl3) δ −102.58. MS = 305.0 (EI). N-4-Chlorobenzoylsaccharin (1e).18c Yield 94% (0.91 g). White solid. 1H NMR (500 MHz, CDCl3) δ 8.17−8.16 (d, J = 7.7 Hz, 1 H), 8.04−8.03 (d, J = 4.1 Hz, 2 H), 7.98−7.94 (m, 1 H), 7.74−7.73 (d, J = 8.3 Hz, 2 H), 7.51−7.50 (d, J = 8.4 Hz, 2 H). 13C NMR (125 MHz, CDCl3) δ 165.4, 157.5, 140.6, 138.5, 136.6, 135.0, 131.9, 131.0, 128.9, 126.5, 125.4, 121.3. MS = 321.0 (EI). N-4-Bromobenzoylsaccharin (1f). New Compound. Yield 85% (0.94 g). White solid. mp = 191−193 °C. 1H NMR (500 MHz, CDCl3) δ 8.17−8.15 (d, J = 7.7 Hz, 1 H), 8.04−8.03 (d, J = 4.1 Hz, 2 H), 8.03−8.01 (d, J = 8.5 Hz, 1 H), 7.98−7.94 (m, 1 H), 7.71−7.70 (d, J = 8.3 Hz, 1 H), 7.69−7.64 (m, 2 H). 13C NMR (125 MHz, CDCl3) δ 165.6, 157.4, 138.5, 136.6, 135.0, 132.4, 131.9, 131.0, 129.2, 126.5, 125.4, 121.3. MS = 364.9 (EI). HRMS calcd for C14H9BrO4NS (M+ + H) 365.9430, found 365.9428. N-4-Methoxycarbonylbenzoylsaccharin (1g).18c Yield 91% (0.94 g). White solid. 1H NMR (500 MHz, CDCl3) δ 8.24−8.23 (d, J = 7.7 Hz, 1 H), 8.19−8.17 (d, J = 8.3 Hz, 2 H), 8.16−8.14 (d, J = 7.8 Hz, 1 H), 8.05−8.04 (d, J = 3.4 Hz, 2 H), 7.82−7.80 (d, J = 8.3 Hz, 2 H), 3.99 (s, 3 H). 13C NMR (125 MHz, CDCl3) δ 165.9, 157.2, 138.5, 136.6, 135.1, 134.4, 130.5, 130.1, 129.6, 129.2, 126.5, 125.3, 121.4, 52.6. MS = 345.0 (EI). N-4-Nitrobenzoylsaccharin (1h).18c Yield 87% (0.87 g). White solid. 1H NMR (500 MHz, CDCl3) δ 8.39−8.37 (d, J = 8.7 Hz, 2 H), 8.17−8.16 (d, J = 7.7 Hz, 1 H), 8.08−8.07 (d, J = 3.6 Hz, 2 H), 8.00− 7.97 (m, 1 H), 7.91−7.89 (d, J = 8.7 Hz, 2 H). 13C NMR (125 MHz, CDCl3) δ 165.0, 162.6, 138.4, 137.9, 136.9, 135.2, 133.9, 130.1, 126.7, 125.0, 123.6, 121.5. MS = 332.0 (EI). N-2-Fluorobenzoylsaccharin (1i).18c Yield 83% (0.76 g). White solid. 1H NMR (500 MHz, CDCl3) δ 8.15−8.13 (d, J = 7.7 Hz, 1 H), 8.06−8.01 (m, 2 H), 7.96−7.93 (t, J = 6.7 Hz, 1 H), 7.72−7.69 (t, J = 7.5 Hz, 1 H), 7.65−7.61 (m, 1 H), 7.36−7.33 (t, J = 7.6 Hz, 1 H), 7.18−7.14 (t, J = 9.6 Hz, 1 H). 13C NMR (125 MHz, CDCl3) δ 162.5, 157.7 (d, J1 = 266.4 Hz), 138.5, 136.6, 134.8, 134.8, 130.7 (d, J3 = 1.5 Hz), 126.5, 125.2, 124.8, 124.7, 121.3, 115.9 (d, J2 = 21.2 Hz). 19F NMR (471 MHz, CDCl3) δ −112.53. MS = 305.0 (EI). N-2-Methylbenzoylsaccharin (1j).18c Yield 95% (0.87 g). White solid. 1H NMR (500 MHz, CDCl3) δ 8.10−8.09 (d, J = 7.7 Hz, 1 H), 8.04−8.00 (m, 2 H), 7.94−7.91 (t, J = 6.2 Hz, 1 H), 7.50−7.47 (t, J = 7.6 Hz, 1 H), 7.43−7.42 (d, J = 7.6 Hz, 1 H), 7.34−7.30 (m 2 H). 13C NMR (125 MHz, CDCl3) δ 166.9, 156.8, 138.4, 136.6, 135.0, 133.1, 131.8, 130.9, 127.7, 126.4, 125.7, 125.3, 121.3, 19.39. MS = 301.0 (EI). (E)-Butyl Cinnamate (3a).11 According to the general procedure, the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (3 mol %) and n-butyl acrylate (2.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 82% yield (33.5 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =15.46 min. 1H NMR (500 MHz, CDCl3) δ 7.72−7.69 (d, J = 16.0 Hz, 1 H), 7.56−7.55 (d, J = 4.9 Hz, 2 H), 7.41−7.40 (t, J = 1.9 Hz, 3 H), 6.49−6.45 (d, J = 15.9 Hz, 1 H), 4.25−4.23 (t, J = 6.6 Hz, 2 H), 1.75−1.69 (m, 2 H), 1.51−1.43 (m, 2 H), 1.01−0.98 (t, J = 7.4 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 167.1, 144.6, 134.5, 130.2, 128.9, 128.1, 118.3, 64.5, 30.8, 19.2, 13.8. MS = 204.1 (EI). (E)-Butyl 3-(4-methoxyphenyl)acrylate (3b).25 According to the general procedure, the reaction of N-4-methoxylbenzoylsaccharin (0.20 mmol), PdCl2 (3 mol%) and n-butyl acrylate (2.0 equiv) in Nmethyl-2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after

workup and chromatography the title compound in 73% yield (34.2 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =17.36 min. 1H NMR (500 MHz, CDCl3) δ 7.68−7.65 (d, J = 16.0 Hz, 1 H), 7.51− 7.49 (d, J = 8.7 Hz, 2 H), 6.94−6.92 (d, J = 8.6 Hz, 2 H), 6.35−6.32 (d, J = 16.0 Hz, 1 H), 4.24−4.21 (t, J = 6.7 Hz, 2 H), 3.86 (s, 3 H), 1.74−1.68 (m, 2 H), 1.50−1.43 (m, 2 H), 1.00−0.97 (t, J = 7.4 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 167.5, 161.3, 144.2, 129.7, 127.2, 115.8, 114.3, 64.3, 55.4, 30.8, 19.2, 13.8. MS = 234.1 (EI). (E)-Butyl 3-(4-(Trifluoromethyl)phenyl)acrylate (3c).25 According to the general procedure, the reaction of N-4-trifluoromethylbenzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 78% yield (42.5 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =13.99 min. 1H NMR (500 MHz, CDCl3) δ 7.73−7.70 (d, J = 16.1 Hz, 1 H), 7.68−7.64 (t, J = 9.3 Hz, 4 H), 6.55−6.52 (d, J = 16.1 Hz, 1 H), 4.27−4.24 (t, J = 6.6 Hz, 2 H), 1.75−1.70 (m, 2 H), 1.51−1.43 (m, 2 H), 1.01−0.98 (t, J = 7.4 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 166.5, 142.7, 137.9, 131.7 (q, J2 = 32.5 Hz), 128.2, 125.9 (q, J3 = 3.7 Hz), 123.8 (q, J1 = 270.4 Hz), 120.9, 64.8, 30.7, 19.2, 13.8. 19F NMR (471 MHz, CDCl3) δ −62.86. MS = 272.1 (EI). (E)-Butyl 3-(4-Fluorophenyl)acrylate (3d).25 According to the general procedure, the reaction of N-4-fluorobenzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 69% yield (30.7 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =14.74 min. 1H NMR (500 MHz, CDCl3) δ 7.68−7.65 (d, J = 16.0 Hz, 1 H), 7.55−7.52 (t, J = 7.5 Hz, 2 H), 7.12−7.08 (t, J = 8.3 Hz, 2 H), 6.40−6.37 (d, J = 16.0 Hz, 1 H), 4.25−4.22 (t, J = 6.6 Hz, 2 H), 1.74−1.68 (m, 2 H), 1.50− 1.43 (m, 2 H), 1.00−0.97 (t, J = 7.4 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 167.0, 163.9 (d, J1 = 249.0 Hz), 143.3, 130.7, 129.9 (d, J3 = 8.5 Hz), 118.1 (d, J4 = 2.3 Hz), 116.0 (d, J2 = 21.7 Hz), 64.5, 30.8, 19.2, 13.8. 19F NMR (471 MHz, CDCl3) δ −109.78. MS = 222.1 (EI). (E)-Butyl 3-(4-Chlorophenyl)acrylate (3e).25 According to the general procedure, the reaction of N-4-chlorobenzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 72% yield (34.4 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =16.51 min. 1H NMR (500 MHz, CDCl3) δ 7.66−7.63 (d, J = 16.0 Hz, 1 H), 7.49−7.47 (d, J = 8.0 Hz, 2 H), 7.39−7.37 (d, J = 8.0 Hz, 2 H), 6.45−6.42 (d, J = 16.1 Hz, 1 H), 4.25−4.22 (t, J = 6.6 Hz, 2 H), 1.74−1.68 (m, 2 H), 1.50− 1.42 (m, 2 H), 1.00−0.97 (t, J = 7.3 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 166.9, 143.1, 136.1, 133.0, 129.2, 129.2, 118.9, 64.6, 30.8, 19.2, 13.8. MS = 238.1 (EI). (E)-Butyl 3-(4-Bromophenyl)acrylate (3f).25 According to the general procedure, the reaction of N-4-bromobenzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 63% yield (35.7 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =17.36 min. 1H NMR (500 MHz, CDCl3) δ 7.65−7.61 (d, J = 16.0 Hz, 1 H), 7.55−7.53 (d, J = 8.2 Hz, 2 H), 7.42−7.40 (d, J = 8.3 Hz, 2 H), 6.47−6.43 (d, J = 16.0 Hz, 1 H), 4.25−4.22 (t, J = 6.6 Hz, 2 H), 1.74−1.68 (m, 2 H), 1.50− 1.42 (m, 2 H), 1.00−0.97 (t, J = 7.4 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 166.9, 143.2, 133.4, 132.1, 129.4, 124.5, 119.0, 64.6, 30.8, 19.2, 13.8. MS = 282.0 (EI). (E)-Methyl 4-(3-Butoxy-3-oxoprop-1-en-1-yl)benzoate (3g).25 According to the general procedure, the reaction of N-4-methoxycarbonylbenzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 65% yield (34.1 mg). Colorless oil. 2,1/1,2 > 98:2. E/ Z > 98:2. GC: rt =18.66 min. 1H NMR (500 MHz, CDCl3) δ 8.08− 8.06 (d, J = 7.9 Hz, 2 H), 7.73−7.69 (d, J = 16.1 Hz, 1 H), 7.61−7.60 (d, J = 7.9 Hz, 2 H), 6.56−6.52 (d, J = 16.1 Hz, 1 H), 4.26−4.23 (t, J = 6.6 Hz, 2 H), 3.95 (s, 3 H), 1.74−1.69 (m, 2 H), 1.50−1.43 (m, 2 H), 1.00−0.97 (t, J = 7.4 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 166.6, 12027

DOI: 10.1021/acs.joc.6b02294 J. Org. Chem. 2016, 81, 12023−12030

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The Journal of Organic Chemistry

16.7 Hz, 1 H). 13C NMR (125 MHz, CDCl3) δ 150.6, 133.5, 131.2, 129.1, 127.4, 118.2, 96.4. MS = 129.1 (EI). (E)-Methyl 2-Methyl-3-phenyl Acrylate (3n).11 According to the general procedure, the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and n-butyl methacrylate (2.0 equiv) in N-methyl-2pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 78% yield (34.1 mg). Colorless oil. Selectivity = 5.80:2.20:1.00. E/Z > 98:2. GC: rt = 15.01 min; isomers 13.74, 13.61 min. The minor isomers could not be separated by silica gel chromatography. Data for the major isomer. 1H NMR (500 MHz, CDCl3) δ 7.71−7.42 (s, 1 H), 7.42−7.42 (d, J = 3.4 Hz, 4 H), 7.36−7.33 (m, 1 H), 4.26−4.23 (t, J = 6.6 Hz, 2 H), 2.14 (s, 3 H), 1.76−1.71 (m, 2 H), 1.52−1.44 (m, 2 H), 1.02−0.99 (t, J = 7.2 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 168.8, 138.6, 136.0, 129.7, 129.0, 128.4, 128.2, 64.8, 30.8, 19.3, 14.1, 13.8. MS = 218.1 (EI). (E)-5-Ethyl-1-phenylnon-1-en-3-one (3o).26 According to the general procedure, the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and 2-ethylhexyl acrylate (2.0 equiv) in N-methyl-2pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 75% yield (39.1 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt = 18.02 min. 1H NMR (500 MHz, CDCl3) δ 7.72−7.69 (d, J = 16.0 Hz, 1 H), 7.56−7.55 (d, J = 4.9 Hz, 2 H), 7.41−7.41 (t, J = 3.2 Hz, 3 H), 6.49−6.46 (d, J = 16.0 Hz, 1 H), 4.16−4.14 (t, J = 5.1 Hz, 2 H), 1.70−1.66 (m, 1 H), 1.48−1.42 (m, 2 H), 1.38−1.34 (m, 6 H), 0.97−0.91 (m, 6 H). 13C NMR (125 MHz, CDCl3) δ 167.3, 144.5, 134.5, 130.2, 128.9, 128.1, 118.4, 67.0, 38.9, 30.5, 29.0, 23.9, 23.0, 14.1, 11.1. MS = 260.2 (EI). (E)-Dec-1-en-1-ylbenzene (3p).11 Mixture of isomers. According to the general procedure, N-benzoylsaccharin (0.20 mmol) was reacted with PdCl2 (3 mol%), and 1-decene (2.0 equiv) in N-methyl-2pyrrolidinone (0.25 M) for 18 h at 160 °C. The compound was characterized by GC-MS analysis. The sample was analyzed by 1H NMR (CDCl3, 500 MHz) and GC-MS to obtain conversion, yield and selectivity using internal standard and comparison with authentic samples. Yield =84%. Selectivity =8.44:2.72:5.99:1. GC: rt = 15.45 min; isomers 14.95, 14.51, 14.34 min. MS = 216.2 (EI). For characterization data, see ref 11. (E)-1,2-Diphenylethene (3q).11 According to the general procedure, the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (5 mol%), and styrene (3.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 85% yield (30.6 mg). White solid. 2,1/1,2 = 90.9:9.1. E/Z > 98:2. GC: rt = 15.58 min; isomer 13.81 min. 1H NMR (500 MHz, CDCl3) δ 7.56−7.54 (d, J = 7.7 Hz, 4 H), 7.41−7.38 (t, J = 7.7 Hz, 4 H), 7.31−7.28 (t, J = 7.1 Hz, 2 H), 7.14 (s, 2 H). 13C NMR (125 MHz, CDCl3) δ 137.4, 128.7, 128.7, 127.6, 126.5. MS = 180.1 (EI). (E)-1-Chloro-4-styrylbenzene (3r).11 According to the general procedure, the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (5 mol%), and 4-chlorostyrene (3.0 equiv) in N-methyl-2pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 89% yield (38.2 mg). White solid. 2,1/1,2 = 94.5:5.5. E/Z > 98:2. GC: rt = 16.92 min; isomer 14.72 min. 1H NMR (500 MHz, CDCl3) δ 7.54−7.53 (d, J = 7.7 Hz, 2 H), 7.48−7.46 (d, J = 8.1 Hz, 2 H), 7.41−7.38 (t, J = 7.7 Hz, 2 H), 7.36−7.35 (d, J = 8.2 Hz, 2 H), 7.32−7.29 (t, J = 6.8 Hz, 1 H), 7.13−7.06 (m, 2 H). 13C NMR (125 MHz, CDCl3) δ 137.0, 135.9, 133.2, 129.3, 128.9, 128.8, 127.9, 127.7, 127.4, 126.6. MS = 214.1 (EI). (E)-1-Methoxy-4-styrylbenzene (3s).11 Method 1. According to the general procedure, the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (5 mol%), and 4-methoxystyrene (3.0 equiv) in N-methyl-2pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 79% yield (33.2 mg). White solid. 2,1/1,2 = 81.3:18.7. E/Z > 98:2. GC: rt = 17.67 min; isomer 15.53 min. 1H NMR (500 MHz, CDCl3) δ 7.53−7.51 (d, J = 7.8 Hz, 2 H), 7.49−7.48 (d, J = 8.3 Hz, 2 H), 7.39−7.36 (t, J = 7.6 Hz, 2 H), 7.28−7.25 (t, J = 8.0 Hz, 1 H), 7.11−6.99 (q, J = 16.3 Hz, 2 H), 6.94− 6.92 (d, J = 8.2 Hz, 2 H), 3.86 (s, 3 H). 13C NMR (125 MHz, CDCl3) δ 159.3, 137.7, 130.2, 128.7, 128.2, 127.7, 127.2, 126.6, 126.3, 114.2, 55.4. MS = 210.1 (EI). Method 2. According to the general procedure, the reaction of N-4-methoxylbenzoylsaccharin (0.20 mmol), PdCl2 (5

166.5, 143.1, 138.7, 131.3, 130.1, 127.9, 120.7, 64.7, 52.3, 30.7, 19.2, 13.8. MS = 262.1 (EI). (E)-Butyl 3-(4-Nitrophenyl)acrylate (3h).25 According to the general procedure, the reaction of N-4-nitrobenzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 77% yield (38.4 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =18.78 min. 1H NMR (500 MHz, CDCl3) δ 8.28−8.26 (d, J = 8.4 Hz, 2 H), 7.74−7.71 (d, J = 17.4 Hz, 1 H), 7.71−7.69 (d, J = 8.9 Hz, 2 H), 6.60−6.57 (d, J = 16.0 Hz, 1 H), 4.27−4.25 (t, J = 6.6 Hz, 2 H), 1.75−1.70 (m, 2 H), 1.50−1.43 (m, 2 H), 1.01−0.98 (t, J = 7.5 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 166.1, 148.5, 141.6, 140.6, 128.6, 124.2, 122.6, 64.9, 30.7, 19.2, 13.7. MS = 249.1 (EI). (E)-Butyl 3-(4-Fluorophenyl)acrylate (3i).25 According to the general procedure, the reaction of N-2-fluorobenzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 91% yield (40.5 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =14.21 min. 1H NMR (500 MHz, CDCl3) δ 7.85−7.82 (d, J = 16.2 Hz, 1 H), 7.58−7.55 (t, J = 7.6 Hz, 1 H), 7.40−7.36 (m, 1 H), 7.20−7.17 (t, J = 7.6 Hz, 1 H), 7.14−7.10 (t, J = 9.8 Hz, 1 H), 6.58−6.55 (d, J = 16.2 Hz, 1 H), 4.26− 4.23 (t, J = 6.6 Hz, 2 H), 1.75−1.69 (m, 2 H), 1.50−1.43 (m, 2 H), 1.01−0.98 (t, J = 7.4 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 167.0, 161.4 (d, J1 = 252.3 Hz), 137.2, 131.6 (d, J4 = 8.7 Hz), 129.1 (d, J7 = 2.8 Hz), 124.4 (d, J6 = 3.6 Hz), 122.6 (d, J3 = 11.6 Hz), 120.9 (d, J5 = 6.5 Hz), 116.2 (d, J2 = 21.8 Hz), 64.6, 30.8, 19.2, 13.8. 19F NMR (471 MHz, CDCl3) δ −114.39. MS = 222.1 (EI). (E)-Butyl 3-(o-Tolyl)acrylate (3j).25 According to the general procedure, the reaction of N-2-methylbenzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl-2pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 97% yield (42.4 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt = 15.15 min. 1H NMR (500 MHz, CDCl3) δ 8.02−7.98 (d, J = 15.9 Hz, 1 H), 7.59−7.57 (d, J = 7.7 Hz, 1 H), 7.31−7.28 (t, J = 7.2 Hz, 1 H), 7.25−7.22 (t, J = 6.9 Hz, 2 H), 6.40−6.37 (d, J = 15.9 Hz, 1 H), 4.26−4.23 (t, J = 6.7 Hz, 2 H), 2.47 (s, 3 H), 1.75−1.69 (m, 2 H), 1.51−1.43 (m, 2 H), 1.01−0.98 (t, J = 7.4 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 167.2, 142.3, 137.6, 133.5, 130.8, 130.0, 126.4, 126.3, 119.3, 64.4, 30.8, 19.8, 19.2, 13.8. MS = 218.1 (EI). (E)-Methyl Cinnamate (3k).11 According to the general procedure, the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and methyl acrylate (2.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 81% yield (26.3 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt = 12.56 min. 1H NMR (500 MHz, CDCl3) δ 7.74−7.71 (d, J = 16.0 Hz, 1 H), 7.55−7.55 (d, J = 2.9 Hz, 2 H), 7.42−7.41 (t, J = 2.5 Hz, 3 H), 6.49−6.46 (d, J = 16.0 Hz, 1 H), 3.84 (s, 3 H). 13C NMR (125 MHz, CDCl3) δ 167.5, 144.9, 134.4, 130.3, 128.9, 128.1, 117.8, 51.7. MS = 162.1 (EI). (E)-N-(tert-Butyl)cinnamamide (3l).11 According to the general procedure, the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (5 mol%), and N-(tert-butyl)acrylate (3.0 equiv) in N-methyl-2pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 80% yield (32.6 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt = 16.60 min. 1H NMR (500 MHz, CDCl3) δ 7.61−7.58 (d, J = 15.6 Hz, 1 H), 7.51− 7.50 (d, J = 7.0 Hz, 2 H), 7.40−7.37 (t, J = 6.6 Hz, 3 H), 6.36−6.33 (d, J = 15.5 Hz, 1 H), 5.45 (s, 1 H), 1.46 (s, 9 H). 13C NMR (125 MHz, CDCl3) δ 165.2, 140.3, 135.0, 129.5, 128.8, 127.7, 121.9, 51.5, 28.9. MS = 203.1 (EI). (E)-Cinnamonitrile (3m).11 According to the general procedure, the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and acrylonitrile (2.0 equiv) in N-methyl-2-pyrrolidinone (0.80 mL) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 95% yield (24.6 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt = 12.35 min. 1H NMR (500 MHz, CDCl3) δ 7.49−7.45 (t, J = 11.2 Hz, 5 H), 7.43−7.42 (d, J = 8.2 Hz, 1 H), 5.93−5.90 (d, J = 12028

DOI: 10.1021/acs.joc.6b02294 J. Org. Chem. 2016, 81, 12023−12030

Note

The Journal of Organic Chemistry

analyzed by 1H NMR (CDCl3, 500 MHz) and GC-MS to obtain conversion and yield using internal standard and comparison with authentic samples.

mol%), and styrene (3.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 70% yield (29.4 mg). White solid. 2,1/1,2 = 74.6:25.4. E/Z > 98:2. GC: rt = 17.74 min; isomer 15.58 min. 1H NMR (500 MHz, CDCl3) δ 7.53−7.51 (d, J = 7.8 Hz, 2 H), 7.49−7.48 (d, J = 8.3 Hz, 2 H), 7.39−7.36 (t, J = 7.6 Hz, 2 H), 7.28−7.25 (t, J = 8.0 Hz, 1 H), 7.11−6.99 (q, J = 16.3 Hz, 2 H), 6.94−6.92 (d, J = 8.2 Hz, 2 H), 3.86 (s, 3 H). 13C NMR (125 MHz, CDCl3) δ 159.3, 137.7, 130.2, 128.7, 128.2, 127.7, 127.2, 126.6, 126.3, 114.2, 55.4. MS = 210.1 (EI). (E)-1-Styryl-4-(trifluoromethyl)benzene (3t).11 According to the general procedure, the reaction of N-trifluoromethylbenzoylsaccharin (0.20 mmol), PdCl2 (5 mol%), and styrene (3.0 equiv) in N-methyl-2pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography the title compound in 71% yield (35.2 mg). White solid. 2,1/1,2 = 92.4:7.6. E/Z > 98:2. GC: rt = 14.66 min; isomer 12.34 min. 1H NMR (500 MHz, CDCl3) δ 7.63 (s, 4 H), 7.57−7.56 (d, J = 7.6 Hz, 2 H), 7.43−7.40 (t, J = 7.5 Hz, 2 H), 7.34−7.32 (t, J = 7.3 Hz, 1 H), 7.24−7.13 (q, J = 16.4 Hz, 2 H). 13C NMR (125 MHz, CDCl3) δ 140.8, 136.6, 131.2, 129.3 (q, J2 = 32.5 Hz), 128.8, 128.3, 127.1, 126.8, 126.6, 125.7 (q, J3 = 3.6 Hz), 124.2 (q, J1 = 270.0 Hz). 19F NMR (471 MHz, CDCl3) δ −62.45. MS = 248.1 (EI). (E)-Butyl 3-(4-((E)-Styryl)phenyl)acrylate (3u).27 Method 1. According to the published procedure,5d N-4-bromobenzoylsaccharin (0.20 mmol) was reacted with Pd2(dba)3 (1.5 mol%), P(t-Bu)3HBF4 (3 mol%), Et3N (1.1 equiv), and styrene (2.0 equiv) in 1,4-dioxane (0.25 M) for 12 h at room temperature. The reaction mixture was filtrated, concentrated, and washed with hexanes (10 mL) to afford E(4-styryl)benzoyl-saccharine (97% yield, 75.6 mg). 2,1/1,2 > 98:2. E/Z > 98:2. Without further purification, the thus obtained E-(4styryl)benzoylsaccharin (0.194 mmol) was reacted with PdCl2 (3 mol%) and n-butyl acrylate (2.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M) for 18 h at 160 °C to afford after workup and chromatography the title compound (83% yield, 49.4 mg). White solid. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt = 25.06 min. 1H NMR (500 MHz, CDCl3) δ 7.72−7.68 (d, J = 16.0 Hz, 1 H), 7.55 (s, 6 H), 7.41− 7.38 (t, J = 7.2 Hz, 2 H), 7.32−7.29 (t, J = 7.0 Hz, 1 H), 7.22−7.11 (q, J = 16.4 Hz, 2 H), 6.49−6.46 (d, J = 16.0 Hz, 1 H), 4.26−4.23 (t, J = 6.5 Hz, 2 H), 1.75−1.70 (m, 2 H), 1.51−1.44 (m, 2 H), 1.01−0.98 (t, J = 7.2 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 167.2, 144.0, 139.3, 137.0, 133.7, 130.1, 128.8, 128.5, 128.0, 127.8, 126.9, 126.7, 117.9, 64.5, 30.8, 19.2, 13.8. MS = 306.2 (EI). Method 2. According to the general procedure, the reaction of N-4-bromobenzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and chromatography n-butyl E-(4-bromophenyl)acrylate (63% yield, 35.7 mg). The thus obtained n-butyl E-(4-bromophenyl)acrylate (0.126 mmol) was reacted with Pd2(dba)3 (1.5 mol%), P(t-Bu)3HBF4 (3 mol%), Et3N (1.1 equiv), and styrene (2.0 equiv) in 1,4-dioxane (0.25 M) for 12 h at room temperature according to the previously published procedure.5d The reaction mixture was filtered, concentrated, and washed with hexanes (10 mL) to afforded the title compound (98% yield, 37.9 mg). White solid. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt = 25.06 min. 1H NMR (500 MHz, CDCl3) δ 7.72−7.68 (d, J = 16.0 Hz, 1 H), 7.55 (s, 6 H), 7.41−7.38 (t, J = 7.2 Hz, 2 H), 7.32−7.29 (t, J = 7.0 Hz, 1 H), 7.22−7.11 (q, J = 16.4 Hz, 2 H), 6.49− 6.46 (d, J = 16.0 Hz, 1 H), 4.26−4.23 (t, J = 6.5 Hz, 2 H), 1.75−1.70 (m, 2 H), 1.51−1.44 (m, 2 H), 1.01−0.98 (t, J = 7.2 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 167.2, 144.0, 139.3, 137.0, 133.7, 130.1, 128.7, 128.5, 128.0, 127.8, 126.9, 126.7, 117.9, 64.5, 30.8, 19.2, 13.8. MS = 306.2 (EI). General Procedure for Selectivity Studies. An oven-dried vial equipped with a stir bar was charged with two amide substrates (each 0.2 mmol, 1.0 equiv), PdCl2 (0.03 equiv), olefin substrate (0.5 equiv), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. N-methyl-2pyrrolidinone (0.25 M) was added with vigorous stirring at room temperature, the reaction mixture was placed in a preheated oil bath at 160 °C, and stirred for the indicated time at 160 °C. After the indicated time, the reaction mixture was cooled down to room temperature and diluted with CH2Cl2 (5 mL). The sample was

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.6b02294. 1 H and 13C NMR spectra (PDF)

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AUTHOR INFORMATION

Corresponding Author

*[email protected] ORCID

Guangrong Meng: 0000-0002-3023-0654 Michal Szostak: 0000-0002-9650-9690 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Financial support was provided by Rutgers University. The 500 MHz spectrometer used in this study was supported by the NSF-MRI grant (CHE-1229030).

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REFERENCES

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DOI: 10.1021/acs.joc.6b02294 J. Org. Chem. 2016, 81, 12023−12030

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DOI: 10.1021/acs.joc.6b02294 J. Org. Chem. 2016, 81, 12023−12030